Clinical Trials /

TVEC and Preop Radiation for Sarcoma (8 ml Dose)

NCT04599062

Description:

The purpose of this research study is to determine the safety and tolerability of talimogene laherparepvec when combined with radiation therapy. Approximately 46 people will take part in this study conducted by investigators at the University of Iowa.

Related Conditions:
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: TVEC and Preop Radiation for Sarcoma (8 ml Dose)
  • Official Title: Neoadjuvant Intralesional Injection of Talimogene Laherparepvec With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas

Clinical Trial IDs

  • ORG STUDY ID: 201504731 (8 milliliter dose)
  • NCT ID: NCT04599062

Conditions

  • Soft Tissue Sarcoma

Interventions

DrugSynonymsArms
Talimogene LaherparepvecTreatment

Purpose

The purpose of this research study is to determine the safety and tolerability of talimogene laherparepvec when combined with radiation therapy. Approximately 46 people will take part in this study conducted by investigators at the University of Iowa.

Detailed Description

      This is a single-arm open-label phase Ib and phase II clinical study assessing the safety and
      relative efficacy of concurrent talimogene laherparepvec in combination with radiotherapy in
      patients with soft tissue sarcomas. Patients will be treated with neoadjuvant radiation and
      weekly intratumoral injections of talimogene laherparepvec. Weekly injections of talimogene
      laherparepvec will be continued until surgery. Surgery will be performed 4-6 weeks from the
      end of radiation therapy to allow for resolution of acute toxicities per current standard of
      care.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalTalimogene Laherparepvec in combination with radiotherapy Talimogene Laherparepvec Dose Levels: Dose 0 = talimogene laherparepvec up to 8.0 mL of 108 PFU/mL dosed weekly Dose -1 = talimogene laherparepvec up to 8.0 mL of 108 PFU/mL dosed every 2 weeks
  • Talimogene Laherparepvec

Eligibility Criteria

        Inclusion Criteria:

          -  Subject has provided informed consent.

          -  Histologically confirmed diagnosis of locally advanced STS that is unresectable with
             clear wide margins, for which preoperative radiotherapy is considered appropriate.

        EXAMPLES:

          -  Resectable stage IIB, III, and IV disease that are not suitable for surgically
             resection alone due to inability to achieve clear margins.

          -  Including metastatic (stage IV) disease for which radiotherapy and surgical resection
             are indicated.

          -  Except certain histologic subtypes: GIST, Desmoid, Ewing sarcoma, Kaposi sarcoma, bone
             sarcomas and myxoid liposarcomas (Grade 1).

          -  Previous treatment: prior systemic anti-cancer treatment consisting of chemotherapy,
             immunotherapy, or targeted therapy are allowed provided therapy completed at least 1
             year prior to enrollment.

          -  No prior Talimogene laherparepvec or tumor vaccines allowed.

          -  No prior radiation to the same tumor bed allowed.

               -  Age ≥18 years.

               -  Both men and women of all races and ethnic groups are eligible for this trial.

               -  ECOG performance status ≤1.

               -  Patient must have measurable disease:

          -  Tumor size at least ≥ 5 cm in the longest diameter as measured by CT scan or MRI for
             which radiation is feasible.

               -  Patient must have injectable disease (direct injection or ultrasound guided).

        Exclusion Criteria:

          -  Certain histologic subtypes: GIST, Desmoid, Ewing sarcoma, Kaposi sarcoma bone
             sarcomas and low grade myxoid liposarcomas ( Grade 1).

          -  History or evidence of sarcoma associated with immunodeficiency states (e.g.:
             Hereditary immune deficiency, HIV, organ transplant or leukemia).

          -  Subjects with retroperitoneal and visceral sarcoma.

          -  History or evidence of gastrointestinal inflammatory bowel disease (ulcerative colitis
             or Crohn's disease) or other symptomatic autoimmune disease including, inflammatory
             bowel disease, or history of any poorly controlled or severe systemic autoimmune
             disease (i.e., rheumatoid arthritis, systemic lupus erythematosus, scleroderma, type I
             diabetes, or autoimmune vasculitis).

          -  History of other malignancy within the past 3 years except treated with curative
             intent and no known active disease present and has not received chemotherapy for ≥ 1
             year before enrollment/randomization and low risk for recurrence.

          -  History of prior or current autoimmune disease.

          -  History of prior or current splenectomy or splenic irradiation.

          -  Active herpetic skin lesions

          -  Require intermittent or chronic treatment with an anti-herpetic drug (e.g.,
             acyclovir), other than intermittent topical use.

          -  Any non-oncology vaccine therapies used for the prevention of infectious disease
             within 28 days prior to enrollment and during treatment period.

          -  Concomitant treatment with therapeutic anticoagulants such as warfarin.

          -  Known human immunodeficiency virus (HIV) disease (requires negative test for
             clinically suspected HIV infection).

          -  Acute or chronic hepatitis B or hepatitis C infection (requires negative test for
             clinically suspected hepatitis B or hepatitis C infection).

          -  Evidence of hepatitis B -

               1. Positive HBV surface antigen (indicative for chronic hepatitis B or recent acute
                  hepatitis B).

               2. Negative HBV surface antigen but positive HBV total core antibody (indicative for
                  resolved hepatitis B infection or occult hepatitis B) and detectable copies of
                  HBV DNA by PCR (detectable HBV DNA copies suggest occult hepatitis B).

          -  Evidence of hepatitis C -

             1. Positive HCV antibody and positive HCV RNA by PCR (undetectable RNA copies suggest
             past and resolved hepatitis C infection).

          -  Female subjects who are pregnant or breast-feeding, or planning to become pregnant
             during study treatment and through 3 months after the last dose of study treatment.

          -  Female subjects of childbearing potential or male subjects who are unwilling to use 2
             highly effective methods of contraception during study treatment and through 3 months
             after the last dose of study treatment. See Section 7.5 for more details.

          -  Currently receiving treatment in another investigational device or drug study, or less
             than 30 days since ending treatment on another investigational device or drug
             study(s).

          -  Other investigational procedures while participating in this study that could affect
             the primary objective of the study as determined by the PI are excluded.

          -  Subject previously has entered this study.

          -  Patients who are receiving any other investigational agents.

          -  Evidence of CNS metastases.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to talimogene laherparepvec.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Patients on or requiring immunosuppressive therapies.

          -  Any of the following laboratory abnormalities:

               -  Hemoglobin < 9.0 g/dL

               -  Absolute neutrophil count (ANC) < 1500 per mm3

               -  Platelet count < 100,000 per mm3

               -  Total bilirubin > 1.5 × ULN

               -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN

               -  Alkaline phosphatase > 2.5 × ULN

               -  PT (or INR) and PTT (or aPTT) > 1.5 × ULN

               -  Creatinine > 2.0 × ULN
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame:14 weeks
Safety Issue:
Description:A DLT is defined as any of the following talimogene laherparepvec-related toxicity or related to the combination of talimogene laherparepvec and radiation therapy during treatment and up to 4 weeks after the last talimogene laherparepvec injection: Grade 3 or greater immune-mediated adverse events, Grade 3 or greater allergic reactions, any grade plasmacytoma, any other unexpected grade 3 or greater hematologic or non-hematologic toxicity, with the exceptions of: any grade of alopecia, expected radiation related skin toxicity of any grade, Grade 3 arthralgia or myalgia, brief (< 1 week) grade 3 fatigue, Grade 3 fever, Grade 3 diarrhea or vomiting responding to supportive case.

Secondary Outcome Measures

Measure:Overall Response Rate (ORR) as Measured by RECIST
Time Frame:24 months
Safety Issue:
Description:Overall response rate (ORR) as measured by RECIST 1.1. Complete response is the disappearance of all target lesions.Partial response is a 30% decrease in the sum of the longest dimensions of the target lesions, relative to baseline. Progressive disease is an increase of 20% or more in the sum of the longest dimension of target lesions. Stable disease is a decrease in the tumor size of < 30% or an increase of < 20%..
Measure:Time to Disease Progression (TTP)
Time Frame:24 months
Safety Issue:
Description:TTP is defined as the time from enrollment until objective tumor progression
Measure:Overall Survival Rate (OS) at 5 Years
Time Frame:5 years
Safety Issue:
Description:Subjects will be followed for overall survival rate (OS) at 5 years from the last enrollment

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Varun Monga, MD

Last Updated

October 16, 2020